PCR- Prevalence, Cost, & Risk (6.27.2025) Save

It's the 06/27/2025. This is the RheumNow podcast. Hi. I'm doctor Jack Cush, executive editor of roomnow.com. This week on the podcast, we're gonna talk money, prevalence, risk, and let's begin with aortic aneurysms.

Not really the stuff that rheumatology is made of, but when it happens in GCA, we sort of perk up and say, what? So this is a TriNetX study. As you know, TriNetX is a worldwide database of over a 100,000,000 EMR, patients. They do propensity matching. There's a little bit of funny business going on here, but only they can come up with data like this.

And this is a study of over almost 7,300 GCA patients compared to 265,000 controls. These are biopsy proven GCA patients. The controls they used were a few, one was like tension headache, and they found that GCA patients had a significantly higher risk, a five year risk of aortic aneurysms. Overall, a 3.6 higher risk, and that included a significantly increased risk for both, thoracic, thoracoabdominal, and abdominal aortic aneurysms. They also found that carotid artery stenosis was also significantly increased in GCA patients with a hazard ratio of one point five nine, about a sixty percent increase.

This is why when you diagnose GCA, newly diagnosed, or there's problematic GCA, you need to be doing other imaging. Right? That's a sort of big thing. Let me go right to the actually, I had this listed at the end, but also related to GCA is another report we put up this week, a review of intracranial GCA. GCA usually is an extracranial large vessel vasculitis that we diagnose in a number of different ways.

This is a review, systematic review of a 100 plus studies, three forty patients. They were all elderly, 73, 74 years of age, and in this study of intracranial GCA, stroke was the most common presentation in seventy one percent of people. Overall, stroke is not that common in GCA patients. Studies show three to seven percent is what I read. And the most common vessels involved in GCA intracranially is number one, vertebrobasilar, fifty three percent.

Internal carotids, 49%. Ophthalmic arteries, 14%. Vertebral basilar posterior circulation, turns out the most common area the brain affected was cerebellum. Again, posterior. What kind of presentations?

Motor defects in forty five percent, speech defects in thirty four percent, cerebellar defects in thirty four percent, cognitive and altered level of consciousness, thirteen to fifteen percent. So, again, intracranial does happen. It should be sought after with vascular imaging, both of the aortic arch but also the head when you make these diagnoses. I think this is an important point as we learn more and more about GCA, which is a kind of a hot area of investigation. Another hot area investigation is ILD, RA ILD, and Jeff Sparks and his group looked at the Korean ILD dataset, the CORAIL study, a hundred and thirty eight patients with RA.

It's a prospective study, and a hundred and thirty eight RA patients who had ILD on CT of the chest. The majority of these were UIP as you would expect as the pattern. They followed them for three years, and they looked at progression. Progression was seen in thirty five percent of people. The risk factors for progression were having UIP, having ILD that involves more than ten percent of the lung, low DLCO levels, the use of prednisone, CCP positivity, k l six levels being elevated, that's something we don't do in rheumatology, they do it a lot in pulmonary, k l six, it's commercially available, RA disease activity.

The point of the paper was that you can identify these high risk stratification factors early on, these are all baseline factors, and that might then lend you to either put those people in studies, treat them more aggressively. What's the evidence that treatment affects the outcome in RAILD? The VA cohort looked at this, looking at their patients seen over a fourteen year period, and using a target emulation trial, large data set of RA patients. They look at those who are treated with one drug versus another drug, try to find out what happens as an outcome, and specifically in these patients with RA ILD, who were either treated with rituximab, abatacep, tocilizumab, or tofacitinib, they looked at the RAILD outcomes as either being mortality or a respiratory hospitalization, and when they compared the outcomes to, patients treated with rituximab, there was no difference amongst the four aggressive therapies, biologics and targeted synthetics. Again, rituximab, abatacept, tocilizumab, tofacitinib.

So that either means they're all equally good or they're all equally bad, and which is it? We don't really know. We don't have great studies that tell us. There are some inferential studies that I've covered here in the past, usually from ACR and EULAR that basically say you look at RA patients who are on therapy and not on therapy, aggressive therapies, they generally have better RA ILD outcomes, suggesting there is an effect to aggressive treatment of RA on the ILD outcomes. But again, we definitely need more research in this area.

Another enlightenment this week is the risk of stroke in patients with a seropositive RA. So this is a study from Korea, health claims data, thirteen hundred RA patients who had newly diagnosed stroke that was three point nine percent. Overall, the significantly lower risk of stroke was seen in RA patients treated with either sulfasalazine, a twenty one percent lower risk, or hydroxychloroquine, a seventeen percent lower risk. I can kind of explain that the aspirin moiety in sulfasalazine, the well known sort of anti atherogenic low lipid, low diabetes, low cardiovascular mortality with hydroxychloroquine, maybe why they're having less stroke with those two particular drugs, but an increased risk of stroke if you're on corticosteroids, seventy one percent higher, that's not surprising. But what's surprising was tocilizumab.

IL six use was associated with a higher risk of stroke. Now this is Korean data. There's something going on there with IL six in Asian populations that may not always be applicable to a European or North American population, but they found a three point five fold increased risk of stroke with tocilizumab. Does that mean they're using it last? They're using it in patients who have very high inflammatory markers?

There's something head scratching about that, but them be the data. A study out of The UK looked at the risk of serious infectious events or serious infections. Seventeen thousand newly diagnosed RA patients, ten thousand on methotrexate, forty five on traditional DMARDs, thirteen thousand on steroids. Overall, thirteen hundred had serious infections, that's hospitalizable infections with an SIE rate of three per one hundred patient years. That's kind of what we've been seeing.

Three to nine is the pre biologic historic control. Recent studies that have looked at this show again three to six, three to five per one hundred patient years. And out of those thirteen hundred, there were three hundred and eleven deaths. So it turns out that the best effect was seen with methotrexate, significantly lowered the risk of serious infectious events by twenty eight percent odds ratio, hazard ratio of zero point seven two. Now, studies have shown methotrexate to lower risk, aggressive treatment with TNF inhibitors may lower risk, but in this study, they showed corticosteroids had no effect on risk, you might actually expect an increased risk, with corticosteroids.

So SI, events, I mean serious infectious events, hospitalizable infections, death from infection, was associated with increasing age, being a smoker, current and past, comorbidities, seropositivity high dash 28 scores, and so this is kind of in in line with what we've seen in other serious infection studies. The some numbers from the past week on RheumNow. The incidence of rheumatoid arthritis has increased globally with a thirteen percent increase from 1990 to 2021. The current incidence is almost eighteen million people globally. We know about one point three in The United States.

Globally, eighteen or seventeen point nine million. However, during the same period, fewer people are dying from RA, but the disability adjusted life years have doubled. High socioeconomic factors seem to be the biggest driver of this burden, and it's thought that smoking control policies will probably result in some better outcomes as we go forward. Another global burden of disease study looked at from the UN, United Nations showed that the number of postmenopausal women in the population rose from thirteen point seven percent in 1990 to twenty percent in 2021. That postmenopausal women, for in the same time frame, the incidence of musculoskeletal disease has gone up significantly, driven mainly by increases in RA, osteoarthritis and gout.

And the prevalence numbers would suggest mostly driven by OA, then by gout, and then by RA being least prevalent amongst those three diseases. Osteoarthritis initiative continues to come out with great data. This is a post hoc MRI study of two ten knee OA patients, average age 64, and they looked at those who were treated with intra articular injections of either hyaluronic acid or corticosteroids. And while both populations or both treatments resulted in less pain in these patients, it turns out that corticosteroids had worsening of MRI evidence of OA with corticosteroids, but not with hyaluronic acid as the control. So what was getting worse in this study was basically progression of cartilage lesions, meniscus damage, and bone marrow fatty lesions.

Okay? Interesting, So again, while we do great things symptomatically with these injections, what's the downstream effect of this? Can it worsen disease? And this data is coming from a radiology journal, suggests that it in fact can occur. So, the cost of drugs is changing.

As of March 2025, there were 71 biosimilars, 15 of them being interchangeable. The majority of those are, like, 60% in the oncology world, about 40% in the rheumatology inflammatory disease world. In The US and in The EU, biosimilars accounted for about $22,600,000,000 in sales in 2025 2024. Twenty two point six billion in biosimilar sales in 2024. The projected increase by 2023 is by at least 25%, and it could go as high as a 171,000,000,000 by 2023 2033.

Excuse me. Another study actually coming out of, the JAMA Dermatology Journal that it looked at a cross sectional analysis of almost seventy six thousand psoriatic arthritis patients taking biologics, TNF inhibitors, IL-twelve twenty three inhibitors, IL-seventeen, IL-twenty three inhibitors, and they saw that the biologics cost averaged $21,000 per annum in '20 in 2007, but that by 2021, fourteen years later, it has now gone up to an average of $47,000 per year. So the average cost of these drugs has gone up, but yet you could still be saving a significant amount of money, if in 2021 you're using the lowest cost drug in the same class. Often that's going be a biosimilar, and you could save up to 44% in the cost of care, at least in taking care of psoriasis. I want to bring to your attention two things about scleroderma, you know, we all struggle with scleroderma.

There's a nice dermatology, teaching aid, in JAMA Dermatology, you can get the link and download it and hand out to patients, that might help. But I was particularly, encouraged by EMA, the European, Medicines Agency, the FDA equivalent for the EU, has come up with a concept paper as asking for commentary and guidance to form, a guidance document for future scleroderma systemic sclerosis trials. They want to be state of the art, they want to promote studies in systemic sclerosis. So they've identified potential study designs, potential endpoints, what kind of exploratory and confirmatory trials are needed, what are the safety and efficacy outcomes that they're looking at, but if you're a scleroderma researcher you need to look at that and maybe have input into that because we certainly do need your guidance to further the development of drugs that will affect the outcome in probably our most devastating disease, and that is systemic sclerosis. A few more reports that are head scratchers.

Secukinumab and uveitis, I was up to the opinion based on some clinical trial data that secukinumab may prevent uveitis and it might be a good drug to use in the presence of uveitis. I think this is now unclear based on a post hoc study of 11 secukinumab randomized clinical trials that found that there was a lower risk of uveitis in ACT SPA studies. So the incidence rates when you're using secukinumab one hundred and fifty milligrams was one point two nine per one 100 patient years versus the placebo control one point seven two. That's kind of what I remembered, but wait a second, that's not true in psoriatic arthritis. Again, they're looking at a lot of patients here, there are about two thousand in both studies.

Secukinumab getting usual dose in psoriatic arthritis of three hundred milligrams, the rate is lower than in spondylitis, it's zero point seven one per one 100 patient years compared to zero in the placebo population. So it was higher, but it was zero in the placebo population. So is that really not as good, or is that an anomaly related to a zero percent uveitis rate in those secukinumab psoriatic arthritis studies where the people got placebo had no uveitis? I don't know, a head scratcher. I might think twice about secukinumab as an option in these patients going forward.

I'm going to end with two reports I thought were interesting. HLA B27, testing in practice, this comes from, I believe the Brigham, and they in their, collective experience of almost 2,000 tests being done, the majority of these tests were being ordered by rheumatology, forty percent of them, ophthalmology twenty one percent. Overall eleven percent of the tests were positive for B27, and the most common indications for ordering the tests were either peripheral arthritis a third, uveitis suspected uveitis in twenty two percent, and low back pain in almost seventeen percent. The strange, fact here is that, seventy percent of these tests where b twenty seven is ordered, and seventy percent of them other autoantibodies and serologies are also being ordered, suggesting a non intelligent approach to diagnoses, meaning people are ordering batteries of tests collectively, or multiple tests at the same time, sometimes that's intelligent, but when you see lots of tests being ordered, maybe it's not. So again, what's the best way to order b 27?

The good news is that when b twenty seven was ordered and was positive, such people were more likely to be referred to rheumatology, thirty fifty three percent versus thirty two percent, that being significant. You know, from what I remember about testing and with B27 is if the patient has ankylosing spondylitis by exam and history, you don't need B27, right? And if they have no chance of having spondylitis, there is no point in ordering B27. It is not a good screening test. So they got itchy teeth and a funky looking toenail, there is no chance that that is going to be spondylitis, and ordering b twenty seven makes no sense.

It's really the in betweeners that a b twenty seven may have clinical utility and increase the likelihood ratio and have a better positive predictive value when you're ordering it in someone who has risk. The last one was again the stat really oh, I already did that report about intracranial GCA. I thought that was really neat, and that was published this week from, I believe, from ARD. If you haven't listened to all our coverage on, EULAR, you should. The last and go from the last one backwards.

EULAR twenty twenty five roundup, doctor Cavanaugh and I, give you almost a fifty five minute review of the meeting. Last week's podcast on innovations and trends from Barcelona, I think is a good one. If you're looking to round out your understanding of what happened at EULAR twenty twenty five, you can either look at the daily recap videos or podcasts, or look at the topic panels for RA, PSA, and SPA. Good discussions, relatively short. There's about eight total podcasts you could listen to and learn everything about EULAR twenty twenty five.

Tune in next week. We'll have more good information for you on roomnow.com. Take care.